Salt tolerance in Aster tripolium L. II. Ionic regulation.
Measurements of tissue ion contents (Na, K and Cl) were carried out at frequent intervals on plants of Aster tripolium L. grown at a range of salinities for 36 d. Aster tripolium behaved as a typical halophyte showing high levels of inorganic ion accumulation even at low salinities. As salinity increased Na replaced K to a large extent in the shoot but root K was unaffected up to 500 mol m-3 external NaCl. Shoot (Na + K) concentration on a tissue water basis was maintained constant in all treatments throughout the experiment, whereas shoot (Na + K) on a dry weight basis showed marked fluctuations in some treatments. An increase in (Na + K) per gram dry weight was, however, accompanied by a parallel increase in fresh weight: dry weight (FW : DW) ratio. Transport of (Na + K) to the shoot per unit root weight changed during the experiment in the manner expected, given the observed changes in shoot relative growth rate and FW : DW to result in a constant shoot (Na + K) concentration on a water basis. Chloride was the major balancing anion in the shoot at high salinity, but never accounted for more than 38% of the (Na + K) found in the root tissue. At all salinities (Na + K) salts accounted for the majority of the measured shoot sap osmotic potential. The interactions between salinity, growth, ion transport and osmotic adjustment are discussed.


Raf-kinase inhibitor protein attenuates microglia inflammation in an in vitro model of intracerebral hemorrhage.
Microglia mediated neuroinflammation plays a crucial role in intracerebral hemorrhage (ICH). Raf kinase inhibitor protein (RKIP), a member of the phosphatidylethanolamine-binding protein (PEBP) family, is a negative regulator of inflammatory responses. However, the expression and anti-inflammatory effects of RKIP in microglia after ICH have not been reported. Therefore, in the current study, we investigated the effects of RKIP on inflammatory responses in erythrocyte lysate-treated BV2 microglia. Furthermore, we analyzed the detailed molecular mechanisms underlying the anti-inflammatory effects of RKIP in microglia. Our results showed that the expression level of RKIP was significantly decreased by erythrocyte lysate treatment in BV2 microglia. Overexpression of RKIP inhibited the production of pro-inflammatory molecules. In addition, overexpression of RKIP attenuated neuronal cell death induced by activated microglia. Moreover, RKIP suppressed the activation of NF-κB signaling pathway in erythrocyte lysis-treated BV2 cells. In conclusion, these data suggest that overexpression of RKIP attenuated microglia inflammation through inhibiting the NF-κB signaling pathway in erythrocyte lysis-treated BV2 cells. The present study provides evidence that RKIP may be used as an effective molecular target for the treatment of ICH.


Toddler with giant omental cyst, profound anemia, and shock: case report and review of the literature.
Giant greater omental cysts with associated massive hemorrhage are rare. We encountered a 16-month-old boy with a four-day history of acute abdominal pain, distension, and paleness. Physical examination revealed a blood pressure of 74/27 mmHg. No well-defined masses were observed on abdominal palpation. The hemoglobin level on admission was 24 g/L. After initial resuscitation and blood transfusion, a computed tomography (CT) scan was performed, revealing a giant cystic mass with an intracystic hemorrhage. The diagnosis was confirmed via exploratory laparotomy, and the cyst, with the attached partial omentum was removed. Pathological findings revealed a simple cyst originating from the greater omentum. The patient recovered uneventfully and remained well during the two-year follow-up period. We reviewed the literature published over the last 27 years on cases of omental cysts to evaluate demographic characteristics, clinical presentations, complications, diagnostic tool options, and surgical approaches.


A remarkable difference in CO2 hydrogenation to methanol on Pd nanoparticles supported inside and outside of carbon nanotubes.
An obvious difference was found in CO2 hydrogenation to methanol on Pd nanoparticles (NPs) supported inside and outside of carbon nanotubes (CNTs). The turnover frequency of methanol synthesis on the Pd NPs supported inside of CNTs was 3.7 times those supported outside of CNTs. It was found that the amount of Pd(δ+) species inside of CNTs was much higher than that outside of CNTs. We proposed that one of the major reasons for the difference in CO2 hydrogenation to methanol might be relative to the concentration of the Pd(δ+) species.


Sulfonated Holey Graphene Oxide (SHGO) Filled Sulfonated Poly(ether ether ketone) Membrane: The Role of Holes in the SHGO in Improving Its Performance as Proton Exchange Membrane for Direct Methanol Fuel Cells.
Sulfonated holey graphene oxides (SHGOs) have been synthesized by the etching of sulfonated graphene oxides with concentrated HNO3 under the assistance of ultrasonication. These SHGOs could be used as fillers for the sulfonated aromatic poly(ether ether ketone) (SPEEK) membrane. The obtained SHGO-incorporated SPEEK membrane has a uniform and dense structure, exhibiting higher performance as proton exchange membranes (PEMs), for instance, higher proton conductivity, lower activation energy for proton conduction, and comparable methanol permeability, as compared to Nafion 112. The sulfonated graphitic structure of the SHGOs is believed to be one of the crucial factors resulting in the higher performance of the SPEEK/SHGO membrane, since it could increase the local density of the -SO3H groups in the membrane and induce a strong interfacial interaction between SHGO and the SPEEK matrix, which improve the proton conductivity and lower the swelling ratio of the membrane, respectively. Additionally, the proton conductivity of the membrane could be further enhanced by the presence of the holes in the graphitic planes of the SHGOs, since it provides an additional channel for transport of the protons. When used, direct methanol fuel cell with the SPEEK/SHGO membrane is found to exhibit much higher performance than that with Nafion 112, suggesting potential use of the SPEEK/SHGO membrane as the PEMs.


CdSe/ZnS quantum dots induce photodynamic effects and cytotoxicity in pancreatic cancer cells.
To investigate the photodynamic effect of CdSe/ZnS quantum dots (QDs) on pancreatic cancer cells and elucidate the probable mechanisms. The pancreatic cancer cell line SW1990 was treated with different concentrations of CdSe/ZnS QDs (0, 0.5, 1.0, 1.5, 2.0, 2.5 μmol/L), with or without illumination. The viability of SW1990 cells was tested using the Cell Counting Kit-8 (CCK-8) assay. The ultrastructural changes of SW1990 cells were observed by transmission electron microscopy. Apoptosis was detected by nuclear staining and flow cytometry (FCM). Reactive oxygen species (ROS) were measured by dichlorofluorescein diacetate via fluorescence microscopy. Expression of Bax, Bcl-2 and caspase-3 was measured by real-time polymerase chain reaction (PCR) and protein immunoblotting 24 h after SW1990 cells were treated with CdSe/ZnS QDs and illuminated. The CCK-8 assay results showed that both CdSe/ZnS QDs with and without illumination suppressed SW1990 cell proliferation. Cell viability was significantly lower when illuminated or with a longer incubation time and a higher light dose. CdSe/ZnS QDs with illumination caused ultrastructural changes in SW1990 cells, such as organelle degeneration and chromatin condensation and aggregation at the periphery of the nucleus. Fluorescence microscopy and FCM showed that CdSe/ZnS QDs (1.5 μmol/L) with illumination increased SW1990 cell apoptosis (53.2%) and ROS generation compared with no illumination. Real-time PCR showed that expression of Bax and caspase-3 was upregulated and Bcl-2 was downregulated. Immunoblotting results were consistent with real-time PCR results. Inhibition of ROS and apoptosis both attenuated QD-photodynamic-therapy-induced cell death. CdSe/ZnS QDs can be used as a photosensitizer to inhibit SW1990 cell proliferation through ROS generation and apoptotic protein expression regulation.


Coronary artery perforation repair using microcoil embolization.
An 82-year-old woman undergoing percutaneous transluminal coronary angioplasty experienced perforation of the terminal portion of the left anterior descending coronary artery caused by guidewire trauma. The coronary artery perforation was successfully closed using a vascular occlusion system consisting of individual thrombogenic coils delivered to the site. Coronary artery perforation (CAP) during percutaneous transluminal coronary angioplasty (PTCA) has been reported to occur in less than 1% of cases. The incidence seems to be higher with the new interventional devices, e.g., DCA, TEC, and laser CAP may result in pericardial hemorrhage and cardiac tamponade or a coronary artery fistula to either the left or right ventricle. The management of CAP may include prolonged balloon inflations, reversal of anticoagulation, pericardiocentesis, and emergency surgery. Proximal perforations sometimes can be managed with vein covered stents. We describe another option in the treatment of distal CAP using a vascular occlusion system.


Tumor associated PD-L1 expression pattern in microscopically tumor positive sentinel lymph nodes in patients with melanoma.
Characterization of PD-L1 expression within clinically/radiologically negative but microscopically tumor positive sentinel lymph nodes (SLN) is important to our understanding of the relevance of this immune checkpoint pathway for adjuvant therapy. Patients included had primary cutaneous melanoma, Breslow thickness of 2.01-4.0 or >4 mm with or without tumor ulceration (T3a, T3b, T4a, T4b). All patients had microscopically tumor positive SLN. Hematoxylin and eosin (H&E) staining was performed, followed by PD-L1 immunohistochemical (IHC) staining using a preliminary IHC assay with anti-PD-L1 antibody clone 22C3. The slides were separately evaluated by two pathologists (JY and CG). Samples containing metastatic melanoma lesions were scored separately for PD-L1 expression in intratumoral and peritumoral locations, by utilizing two scoring methods. Twenty-four patients where metastatic melanoma presence in the SLN was confirmed by H&E review of the cut sections were included in the final analysis of PD-L1 expression. SLN tumor size ranged from 1 to 2 mm. For three patients, the melanin content was too high to confidently assign a PD-L1 score. For the remaining 21 patients, all had some evidence of either intratumoral or peritumoral PD-L1 expression. The frequency of intratumoral tumor-associated PD-L1 expression was: 0 % of tumor cells (3 pts, 14 %); <1 % (5 pts, 24 %); 1-10 % (6 pts, 29 %) and >10 % (7 pts, 33 %). Tumor-associated PD-L1 expression is readily detectable within melanoma micrometastases in the SLN of the majority of patients. These results support the testing of a therapeutic role for PD1/PD-L1 inhibition in the adjuvant setting, targeting melanoma micrometastases.


Tiron ameliorates oxidative stress and inflammation in titanium dioxide nanoparticles induced nephrotoxicity of male rats.
Although the widespread use of titanium dioxide nanoparticles (TiO2 NPs), few studies were conducted on its hazard influence on human health. Tiron a synthetic vitamin E analog was proven to be a mitochondrial targeting antioxidant. The current investigation was performed to assess the efficacy of tiron against TiO2 NPs induced nephrotoxicity. Eighty adult male rats divided into four different groups were used: group I was the control, group II received TiO2 NPs (100mg\Kg BW), group III received TiO2 NPs plus tiron (470mg\kg BW), and group IV received tiron alone. Urea, creatinine and total protein concentrations were measured in serum to assess the renal function. Antioxidant status was estimated by determining the activities of glutathione peroxidase, superoxide dismutase, malondialdehyde (MDA) level and glutathione concentration in renal tissue. As well as Renal fibrosis was evaluated though measuring of transforming growth factor-β1 (TGFβ1) and matrix metalloproteinase 9 (MMP9) expression levels and histopathological examination. TiO2 NPs treated rats showed marked elevation of renal indices, depletion of renal antioxidant enzymes with marked increase in MDA concentration as well as significant up-regulation in fibrotic biomarkers TGFβ1 and MMP9. Oral administration of tiron to TiO2 NPs treated rats significantly attenuate the renal dysfunction through decreasing of renal indices, increasing of antioxidant enzymes activities, down-regulate the expression of fibrotic genes and improving the histopathological picture for renal tissue. In conclusion, tiron was proved to attenuate the nephrotoxicity induced by TiO2 NPs through its radical scavenging and metal chelating potency.


Immunomodulatory and anti-oxidative effect of the direct TRPV1 receptor agonist capsaicin on Schwann cells.
Only few studies describe the impact of nutritive factors on chronic inflammatory demyelinating polyneuropathy (CIDP), an inflammatory disease of the peripheral nervous system. The active component of chili pepper, capsaicin, is the direct agonist of the transient receptor potential channel vanilloid subfamily member 1. Its anti-inflammatory effect in the animal model experimental autoimmune neuritis (EAN) has been previously demonstrated. In the present study, we describe the anti-inflammatory and anti-oxidative influence of capsaicin on Schwann cells (SCs) in an in vitro setting. Hereby, we analyze the effect of capsaicin on Schwann cells' gene expression pattern, major histocompatibility complex class II (MHC-II) presentation, and H2O2-induced oxidative stress. Furthermore, the effect of capsaicin on myelination was examined in a SC-dorsal root ganglia (DRG) coculture by myelin basic protein staining. Finally, in order to investigate the isolated effect of capsaicin on SCs in EAN pathology, we transplant naïve and capsaicin pre-treated SCs intrathecally in EAN immunized rats and analyzed clinical presentation, electrophysiological parameters, and cytokine expression in the sciatic nerve. In SC monoculture, incubation with capsaicin significantly reduces interferon gamma-induced MHC-II production as well as toll-like receptor 4 and intercellular adhesion molecule 1 mRNA expression. Calcitonin gene-related peptide mRNA production is significantly upregulated after capsaicin treatment. Capsaicin reduces H2O2-induced oxidative stress in SC in a preventive, but not therapeutic setting. In a SC-DRG coculture, capsaicin does not affect myelination rate. After intrathecal transplantation of naïve and capsaicin pre-treated SCs in EAN-immunized rats, naïve, but not capsaicin pre-treated intrathecal SCs, ameliorated EAN pathology in rats. In conclusion, we were able to demonstrate a direct immunomodulatory and anti-oxidative effect of capsaicin in a SC culture by reduced antigen presentation and expression of an anti-inflammatory profile. Furthermore, capsaicin increases the resistance of SCs against oxidative stress. A primary effect of capsaicin on myelination was not proven. These results are in concordance with previous data showing an anti-inflammatory effect of capsaicin, which might be highly relevant for CIDP patients.


2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced cleft palate in the mouse: evidence for alterations in palatal shelf fusion.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes a high percentage of cleft palate in fetuses when administered during organogenesis in certain strains of mice including the C57BL/6J, but not in certain other strains (AKR/J). The purpose of the present study was to examine various biochemical and morphological aspects of TCDD-induced changes in the developing palatal shelves. Our results indicate that when TCDD (100 micrograms/kg) was given on individual days between days 8 and 10 of gestation, a high percentage of cleft palate was observed. Receptors specific for TCDD were detected in the C57BL/6J but not AKR/J palatal shelves. The amount of TCDD receptors is highest in the palatal shelves on day 13 as compared to other embryonic tissues including the liver. Examination of cryostat sections taken from embryos during the time of palatal elevation and fusion demonstrated that TCDD does not interfere with growth, elevation, or initial contact of the palatal shelves, but does interfere with firm adhesion and/or degeneration of the medial epithelial cells. Our results suggest that TCDD exerts a direct effect on the embryonic palatal shelves which results in formation of cleft palate.


Peroperative arterial recanalization with Kensey dynamic angioplasty. Histopathologic studies.
The morphology of occluded superficial femoral artery segments and of particles in the effluent fluid after dynamic Kensey catheter angioplasty was analyzed in six patients treated with an intraoperative retrograde technique. The effluent was collected during the procedure and the arteries were extirpated for microscopy after the recanalization attempt. In three patients with easy recanalization, histologic study showed highly cellular, proliferating connective tissue. In three patients with unsuccessful recanalization, mature, cell-poor connective healing tissue obliterated the lumen. The effluent contained particles measuring 14 to 320 microns, the largest of which had the potential to occlude small arteries. The results of this pilot study are to be regarded as preliminary.


Antibacterial properties and toxicity from metallic nanomaterials.
The era of antibiotic resistance is a cause of increasing concern as bacteria continue to develop adaptive countermeasures against current antibiotics at an alarming rate. In recent years, studies have reported nanoparticles as a promising alternative to antibacterial reagents because of their exhibited antibacterial activity in several biomedical applications, including drug and gene delivery, tissue engineering, and imaging. Moreover, nanomaterial research has led to reports of a possible relationship between the morphological characteristics of a nanomaterial and the magnitude of its delivered toxicity. However, conventional synthesis of nanoparticles requires harsh chemicals and costly energy consumption. Additionally, the exact relationship between toxicity and morphology of nanomaterials has not been well established. Here, we review the recent advancements in synthesis techniques for silver, gold, copper, titanium, zinc oxide, and magnesium oxide nanomaterials and composites, with a focus on the toxicity exhibited by nanomaterials of multidimensions. This article highlights the benefits of selecting each material or metal-based composite for certain applications while also addressing possible setbacks and the toxic effects of the nanomaterials on the environment.


Molecular Detection of Toxoplasma Gondii in Haemaphysalis Ticks in Korea.
Toxoplasma gondii are intracellular protozoa that can cause neurological disease or death in fetuses and even in immunocompromised human adults. Ticks are recognized as vectors of many microorganisms including viruses, bacteria, and protozoa. Recent studies detected T. gondii in various tick species in many countries. In this study, we performed PCR detection of the T. gondii B1 gene from Haemaphysalis ticks collected from vegetation in 4 localities, Wonju, Gunsan, Miryang, and Yangsan, in Korea. We analyzed DNA from 314 ticks (268 Haemaphysalis longicornis and 46 Haemaphysalis flava) and the B1 gene of T. gondii was detected in 13 of these. The detection of T. gondii in ticks differed significantly by region (P=0.021). T. gondii was detected in the following percentages of collected ticks: 3.7% (7 of 189) in Gunsan, 10% (5 of 50) in Wonju, 16.7% (1 of 6) in Yangsan, and 0% (0 of 69) in Miryang. The detection of T. gondii in ticks was not associated with tick species or development stage. This is the first report of T. gondii detection in ticks in Korea. Our results provide important information necessary to understand toxoplasmosis transmission.


Biochemical characterization of a regulatory cascade controlling transcription of the Pseudomonas aeruginosa type III secretion system.
Many Gram-negative pathogens utilize type III secretion systems (T3SS) to translocate effector proteins into eukaryotic host cells. Expression of T3SS genes is highly regulated and is often coupled to type III secretory activity. Transcription of the Pseudomonas aeruginosa T3SS genes is coupled to secretion by a cascade of interacting regulatory proteins (ExsA, ExsD, ExsC, and ExsE). ExsA is an activator of type III gene transcription, ExsD binds ExsA to inhibit transcription, ExsC inhibits ExsD activity, and ExsE inhibits ExsC activity. The entire process is coupled to secretion by virtue of the fact that ExsE is a secreted substrate of the T3SS. Changes in the intracellular concentration of ExsE are thought to govern formation of the ExsC-ExsE, ExsC-ExsD, and ExsD-ExsA complexes. Whereas formation of the ExsC-ExsE complex allows ExsD to bind ExsA and transcription of the T3SS is repressed, formation of the ExsC-ExsD complex sequesters ExsD from ExsA and transcription of the T3SS is induced. In this study, we characterized the self-association states of ExsC, ExsD, and ExsE and the binding interactions of ExsC with ExsE and ExsD. ExsC exists as a homodimer and binds one molecule of ExsE substrate. Dimeric ExsC also interacts directly with ExsD to form a heterotetrameric complex. The difference in binding affinities between the ExsC-ExsE (K(d) 1 nm) and ExsC-ExsD (K(d) 18 nm) complexes supports a model in which ExsC preferentially binds cytoplasmic ExsE, resulting in the inhibition of T3SS gene transcription.


Layer-Output Guided Complementary Attention Learning for Image Defocus Blur Detection.
Defocus blur detection (DBD), which has been widely applied to various fields, aims to detect the out-of-focus or in-focus pixels from a single image. Despite the fact that the deep learning based methods applied to DBD have outperformed the hand-crafted feature based methods, the performance cannot still meet our requirement. In this paper, a novel network is established for DBD. Unlike existing methods which only learn the projection from the in-focus part to the ground-truth, both in-focus and out-of-focus pixels, which are completely and symmetrically complementary, are taken into account. Specifically, two symmetric branches are designed to jointly estimate the probability of focus and defocus pixels, respectively. Due to their complementary constraint, each layer in a branch is affected by an attention obtained from another branch, effectively learning the detailed information which may be ignored in one branch. The feature maps from these two branches are then passed through a unique fusion block to simultaneously get the two-channel output measured by a complementary loss. Additionally, instead of estimating only one binary map from a specific layer, each layer is encouraged to estimate the ground truth to guide the binary map estimation in its linked shallower layer followed by a top-to-bottom combination strategy, gradually exploiting the global and local information. Experimental results on released datasets demonstrate that our proposed method remarkably outperforms state-of-the-art algorithms.


Leukemia: the dentist's role in diagnosis.
Patients with leukemia frequently have oral signs and symptoms that may lead to the early diagnosis of this condition. Hematologic laboratory tests that would be of value include a white blood cell count and a platelet count. The dental practitioner should be aware of those diagnostic signs and the possibilities of oral complications associated with the disease. The nature of leukemia and its complications require a regular and thorough oral examination as part of the routine treatment of these patients.


Comparison of reversal and adverse effects of sugammadex and combination of - Anticholinergic-Anticholinesterase agents in pediatric patients.
We aimed to compare clinical effects of sugammadex versus combination of anticholinergic-anticholinesterase agents for reversing of nondepolarizing neuromuscular block in pediatric patients. A total of 60 pediatric patients whom should be performed general anesthesia in the supine position were enrolled to this randomized double-blinded clinical trial. Fentanyl 1 μg/kg, propofol 2 mg/kg, rocuronium 0.6 mg/kg were used in induction and sevofluran, 50% O2-50% N2O in maintenance of anesthesia. Neuromuscular conductions were assessed by train of four (TOF)-Watch SX (Organon, Schering-Plough, Ireland) acceleromyograph. Patients were intubated at the moment of TOF 0. At the end of the operation emergence of T2 point was replied by 2 mg/kg sugammadex administration in group 1 and 0.06 mg/kg neostigmine +0.02 mg/kg atropine in group 2. At the moment of T0.9 inhalation, gases were ceased, and patients were extubated. Hemodynamic alterations, access to T0.9, extubation time, recovery parameters, drug consumptions and adverse effects were recorded. Train of four scores showed a lesser increase in group 2 than group 1 from 15(th) s to 30(th) min during post reverse period (from 6.9 ± 6.4 to 91.7 ± 7.2 in group 2 vs. from 35.4 ± 21.4 to 99.5 ± 1.0 in group 1) (p < 0.0004). Group 1 patients exhibited much more complete muscle strength rates than group 2 (P < 0.001). T0.9 and extubation times were significantly longer in group 2 than group 1 (P < 0.001). Comparison of adverse effects yielded no difference. Sugammadex can be considered as a safe agent in order to reverse neuromuscular block in pediatric patients.


Comparative Antimicrobial Efficacy of Two Hand Sanitizers in Intensive Care Units Common Areas: A Randomized, Controlled Trial.
OBJECTIVE Contaminated hands of healthcare workers (HCWs) are an important source of transmission of healthcare-associated infections. Alcohol-based hand sanitizers, while effective, do not provide sustained antimicrobial activity. The objective of this study was to compare the immediate and persistent activity of 2 hand hygiene products (ethanol [61% w/v] plus chlorhexidine gluconate [CHG; 1.0% solution] and ethanol only [70% v/v]) when used in an intensive care unit (ICU). DESIGN Prospective, randomized, double-blinded, crossover study SETTING Three ICUs at a large teaching hospital PARTICIPANTS In total, 51 HCWs involved in direct patient care were enrolled in and completed the study. METHODS All HCWs were randomized 1:1 to either product. Hand prints were obtained immediately after the product was applied and again after spending 4-7 minutes in the ICU common areas prior to entering a patient room or leaving the area. The numbers of aerobic colony-forming units (CFU) were compared for the 2 groups after log transformation. Each participant tested the alternative product after a 3-day washout period. RESULTS On bare hands, use of ethanol plus CHG was associated with significantly lower recovery of aerobic CFU, both immediately after use (0.27 ± 0.05 and 0.88 ± 0.08 log10 CFU; P = .035) and after spending time in ICU common areas (1.81 ± 0.07 and 2.17 ± 0.05 log10 CFU; P<.0001). Both the antiseptics were well tolerated by HCWs. CONCLUSIONS In comparison to the ethanol-only product, the ethanol plus CHG sanitizer was associated with significantly lower aerobic bacterial counts on hands of HCWs, both immediately after use and after spending time in ICU common areas. CLINICAL TRIAL IDENTIFIER Clinicaltrials.gov identifier NCT02258412 Infect Control Hosp Epidemiol 2018;39:267-271.


Whipple's disease.
Whipple's disease is a chronic systemic bacterial infection that predominantly affects middle-aged men. Antimicrobial therapy is curative. The causative agent has been identified as Tropheryma whippelii. A PCR-based diagnostic test is now available and is particularly useful in patients with early-stage or atypical disease. The test can detect bacterial nucleic acids in tissues and body fluids, including joint fluid. Studies using this test found no evidence that T. whippelii may be a common cause of unexplained seronegative oligoarthritis or polyarthritis. Further work is needed to identify the patient subsets most likely to benefit from T. whippelii PCR testing in joint specimens. Isolation of the organism has been achieved recently. This will probably allow development of a serological test, which may facilitate the diagnosis. Weight loss and diarrhea are the most common symptoms of Whipple's disease. Joint manifestations antedate the intestinal complaints in three-fourths of patients, the mean interval being 6 years. In most patients, duodenal and jejunal biopsy specimens contain macrophages filled with PAS-stained granules corresponding to bacteria. Nevertheless, some patients have no intestinal symptoms, and a few have normal intestinal histological findings. Before the onset of intestinal symptoms, several clinical patterns should suggest Whipple's disease. Unexplained, chronic, seronegative oligoarthritis or polyarthritis affecting the large limb joints is the most common presentation. A characteristic feature is the intermittent occurrence of the joint manifestations, at least early in the disease. Other patterns are destructive polyarthritis and spondyloarthropathy. The major advances made recently in techniques for detecting and isolating the causative agent may show that Whipple's disease is more common and has a broader clinical spectrum than was previously thought. Another hope is that the diagnosis will be made earlier, before the development of potentially fatal systemic complications.


Habitat geography around Hawaii's oceanic islands influences tiger shark (Galeocerdo cuvier) spatial behaviour and shark bite risk at ocean recreation sites.
We compared tiger shark (Galeocerdo cuvier) spatial behaviour among 4 Hawaiian Islands to evaluate whether local patterns of movement could explain higher numbers of shark bites seen around Maui than other islands. Our sample consisted of 96 electronically-tagged (satellite and acoustic transmitters) tiger sharks, individually tracked for up to 6 years. Most individuals showed fidelity to a specific 'home' island, but also swam between islands and sometimes ranged far (up to 1,400 km) offshore. Movements were primarily oriented to insular shelf habitat (0-200 m depth) in coastal waters, and individual sharks utilized core-structured home ranges within this habitat. Core utilization areas of large tiger sharks were closer to high-use ocean recreation sites around Maui, than around Oahu. Tiger sharks routinely visited shallow ocean recreation sites around Maui and were detected on more days overall at ocean recreation sites around Maui (62-80%) than Oahu (<6%). Overall, our results suggest the extensive insular shelf surrounding Maui supports a fairly resident population of tiger sharks and also attracts visiting tiger sharks from elsewhere in Hawaii. Collectively these natural, habitat-driven spatial patterns may in-part explain why Maui has historically had more shark bites than other Hawaiian Islands.


Cancer patient experience with navigation service in an urban hospital setting: a qualitative study.
Cancer patient navigators are increasingly present on the oncology health care team. The positive impact of navigation on cancer care is recognised, yet a clear understanding of what the patient navigator does and how he/she executes the role continues to emerge. This study aimed to understand cancer patients' perceptions of, and experiences with patient navigation, exploring how navigation may enhance the patient experience in an urban hospital setting where patients with varying needs are treated. A qualitative study using a constructionist approach was conducted. Fifteen colorectal cancer patients participated in semi-structured telephone interviews. Data were analyzed inductively and iteratively. Findings provide insight into two central aspects of cancer navigation: navigation as patient-centred coordination and explanation of clinical care, and navigation as individualised, holistic support. Within these themes, the key benefits of navigation from the patients' perspective were demystifying the system; ensuring comprehension, managing expectations; and, delivering patient-centred care. The navigator provided individualised and extended family support; a holistic approach; and, addressed emotional and psychological needs. These findings provide a means to operationalise and validate an emerging role description and competency framework for the cancer navigator who must identify and adapt to patients' varying needs throughout the cancer care continuum.


Green Synthesis and Characterization of Novel Silver Nanoparticles Using Achillea maritima subsp. maritima Aqueous Extract: Antioxidant and Antidiabetic Potential and Effect on Virulence Mechanisms of Bacterial and Fungal Pathogens.
Novel silver nanoparticles were synthesized based on a simple and non-toxic method by applying the green synthesis technique, using, for the first time, the aqueous extract of an extremophile plant belonging to the Achillea maritima subsp. maritima species. AgNP characterization was performed via UV-Visible, front-face fluorescence spectroscopy, and FTIR and XRD analyses. AgNP formation was immediately confirmed by a color change from yellow to brown and by a surface plasmon resonance peak using UV-Vis spectroscopy at 420 nm. The biosynthesized AgNPs were spherical in shape with a size ranging from approximatively 14.13 to 21.26 nm. The presented silver nanoparticles exhibited strong antioxidant activity following a DPPH assay compared to ascorbic acid, with IC50 values of about 0.089 µg/mL and 22.54 µg/mL, respectively. The AgNPs showed higher antidiabetic capacities than acarbose, by inhibiting both alpha amylase and alpha glucosidase. The silver nanoparticles could affect various bacterial mechanisms of virulence, such as EPS production, biofilm formation and DNA damage. The silver nanoparticles showed no lysozyme activity on the cell walls of Gram-positive bacteria. The AgNPs also had a strong inhibitory effect on the Candida albicans virulence factor (extracellular enzymes, biofilm formation). The microscopic observation showed abnormal morphogenesis and agglomeration of Candida albicans exposed to AgNPs. The AgNPs showed no cytotoxic effect on human cells in an MTT assay. The use of novel silver nanoparticles is encouraged in the formulation of natural antimicrobial and antidiabetic agents.


Effects of metformin on apoptosis and α-synuclein in a rat model of pentylenetetrazole-induced epilepsy.
The present study was designed to examine the possible neuroprotective and antiepileptic effects of metformin (Metf) in a rat model of pentylenetetrazole (PTZ)-induced epilepsy and its possible underlying mechanisms. Forty male albino rats were assigned to 4 groups of equal size: (1) normal control (NC) group, (2) Metf group: daily treatment with Metf (200 mg/kg, i.p.) for 2 weeks, (3) PTZ group: treatment with PTZ (50 mg/kg, i.p.) every other day for 2 weeks, and (4) Metf + PTZ group: daily treatment with PTZ and metformin (200 mg/kg, i.p.) for 2 weeks. Administration of PTZ caused a significant increase in seizure score and duration, induced a state of oxidative stress (high malondialdehyde, low reduced glutathione and catalase activity), and led to the upregulation of β-catenin, caspase-3, and its cleavage products, Hsp70 and α-synuclein, in hippocampal regions as well as a significant reduction in seizure latency. While Metf treatment significantly ameliorated PTZ-induced seizures, attenuated oxidative stress, and upregulated α-synuclein and β-catenin expression, it also inhibited caspase-3 activation and the release of the cleavage product and caused more upregulation in Hsp70 expression in hippocampal regions (p < 0.05). In conclusion, the antiepileptic and neuroprotective effects of Metf in PTZ-induced epilepsy might be due to the inhibition of apoptosis, attenuation of oxidative stress and α-synuclein expression, and upregulation of Hsp70.


Physiological and Proteomic Responses of Continuous Cultures of Microcystis aeruginosa PCC 7806 to Changes in Iron Bioavailability and Growth Rate.
The hepatotoxin microcystin (MCYST) is produced by a variety of freshwater cyanobacterial species, including Microcystis aeruginosa Interestingly, MCYST-producing M. aeruginosa strains have been shown to outcompete their nontoxic counterparts under iron-limiting conditions. However, the reasons for this are unclear. Here we examined the proteomic response of M. aeruginosa PCC 7806 continuous cultures under different iron and growth regimes. Iron limitation was correlated with a global reduction in levels of proteins associated with energy metabolism and photosynthesis. These proteomic changes were consistent with physiological observations, including reduced chlorophyll a content and reduced cell size. While levels of MCYST biosynthesis proteins did not fluctuate during the study period, both intra- and extracellular toxin quotas were significantly higher under iron-limiting conditions. Our results support the hypothesis that intracellular MCYST plays a role in protecting the cell against oxidative stress. Further, we propose that extracellular MCYST may act as a signaling molecule, stimulating MCYST production under conditions of iron limitation and enhancing the fitness of bloom populations. Microcystin production in water supply reservoirs is a global public health problem. Understanding the ecophysiology of hepatotoxic cyanobacteria, including their responses to the presence of key micronutrient metals such as iron, is central to managing harmful blooms. To our knowledge, this was the first study to examine proteomic and physiological changes occurring in M. aeruginosa continuous cultures under conditions of iron limitation at different growth rates.


Oxidation State 10 Exists.
In a recent paper, Wang et al. found an iridium-containing compound with a formal oxidation state of 9. This is the highest oxidation state ever found in a stable compound. To learn if this is the highest chemical oxidation state possible, Kohn-Sham density functional theory was used to study various compounds, including PdO4 (2+) , PtO4 (2+) , PtO3 F2 (2+) , PtO4 OH(+) , PtO5 , and PtO4 SH(+) , in which the metal has an oxidation state of 10. It was found that PtO4 (2+) has a metastable state that is kinetically stable with a barrier height for decomposition of 31 kcal mol(-1) and a calculated lifetime of 0.9 years. All other compounds studied would readily decompose to lower oxidation states.


Experimental demonstration of X-ray drive enhancement with rugby-shaped hohlraums.
Rugby-shaped hohlraums have been suggested as a way to enhance x-ray drive in the indirect drive approach to inertial confinement fusion. This Letter presents an experimental comparison of rugby-shaped and cylinder hohlraums used for D2 and D3He-filled capsules implosions on the Omega laser facility, demonstrating an increase of x-ray flux by 18% in rugby-shaped hohlraums. The highest yields to date for deuterium gas implosions in indirect drive on Omega (1.5x10{10} neutrons) were obtained, allowing for the first time the measurement of a DD burn history. Proton spectra measurements provide additional validation of the higher drive in rugby-shaped hohlraums.


Māori and Pacific people in New Zealand have a higher risk of hospitalisation for COVID-19.
We aim to quantify differences in clinical outcomes from COVID-19 infection in Aotearoa New Zealand by ethnicity and with a focus on risk of hospitalisation. We used data on age, ethnicity, deprivation index, pre-existing health conditions and clinical outcomes on 1,829 COVID-19 cases reported in New Zealand. We used a logistic regression model to calculate odds ratios for the risk of hospitalisation by ethnicity. We also considered length of hospital stay and risk of fatality. After controlling for age and pre-existing conditions, we found that Māori have 2.50 times greater odds of hospitalisation (95% CI 1.39-4.51) than non-Māori non-Pacific people. Pacific people have three times greater odds (95% CI 1.75-5.33). Structural inequities and systemic racism in the healthcare system mean that Māori and Pacific communities face a much greater health burden from COVID-19. Older people and those with pre-existing health conditions are also at greater risk. This should inform future policy decisions including prioritising groups for vaccination.


Characterization of cardiac arrest in the emergency department of a Brazilian University Reference Hospital: A prospective study.
Sudden cardiac arrest (CA) represents one of the greatest challenges for medicine due to the vast number of cases and its social and economic impact. Despite advances in cardiopulmonary resuscitation (CPR) techniques, mortality rates have not significantly decreased over decades. This study was undertaken to characterize patients that have suffered CA and to identify factors related to mortality. This prospective study was conducted at Emergency Department of São Paulo Hospital, Brazil. Two hundred and eighty five patients were followed for one year after treatment for CA. The mean age was 66.3±17.2 yr, and they were predominantly male (55.8%) and Caucasian (71.9%). Mortality rate and factors associated with mortality were the primary and secondary outcome measures. Data were collected using an in-hospital Utstein-style report. A logistic regression analysis was used to determine which variables were related to mortality. Regarding the characteristics of CPR, 76.5 per cent occurred in hospital, respiratory failure was the most common presumed immediate cause of CA (30.8%) and pulseless electrical activity was the most frequent initial rhythm (58.7%). All attempts at CPR utilized chest compressions and ventilation and the most utilized interventions were epinephrine (97.2%) and intubation (68.5%). Of all patients treated, 95.4 per cent died. Patients with pulseless electrical activity had a higher risk of death than those patients with ventricular fibrillation. The findings of the study highlighted that the mortality rate among CA patients was high. The variable that best explained mortality was the initial CA rhythm.


Effects of alpha 2-adrenergic blockade on renal hemodynamics in patients with insulin dependent diabetes mellitus.
The role of renal alpha 2-adrenoceptors in the regulation of glomerular filtration and renal perfusion is unknown. We studied the effects of alpha 2-adrenergic blockade on renal hemodynamics in six patients with insulin-dependent diabetes mellitus (IDDM) and in six healthy subjects. At the basal state, glomerular filtration rate (GFR) was higher in IDDM although the difference from control levels was not statistically significant. Volume expansion, achieved by infusion of isotonic sodium chloride solution, during placebo infusion induced a significant drop in GFR in healthy subjects but not in IDDM patients. Infusion of the alpha 2-adrenoceptor antagonist idazoxan did not further modify the effect of volume expansion on GFR. Renal plasma and blood flow as well as filtration fraction were not significantly changed by volume expansion or idazoxan infusion. Plasma renin activity and plasma aldosterone levels decreased during volume expansion in both IDDM and control subjects. In conclusion, volume expansion induced decreased GFR in healthy controls but not in IDDM patients. Since infusion of idazoxan did not affect GFR or other parameters of renal hemodynamics, renal alpha 2-adrenoceptors do not seem to be involved in the regulation of renal function. Hence, enhanced renal alpha 2-adrenoceptor activity is not likely to underlie hyperfiltration as seen in IDDM.


13 C flux analysis of cyanobacterial metabolism.
(13)C metabolic flux analysis (MFA) has made important contributions to our understanding of the physiology of model strains of E. coli and yeast, and it has been widely used to guide metabolic engineering efforts in these microorganisms. Recent advancements in (13)C MFA methodology combined with publicly available software tools are creating new opportunities to extend this approach to examine less characterized microbes. In particular, growing interest in the use of cyanobacteria as industrial hosts for photosynthetic production of biofuels and biochemicals has led to a critical need to better understand how cyanobacterial metabolic fluxes are regulated in response to changes in growth conditions or introduction of heterologous pathways. In this contribution, we review several prior studies that have applied isotopic steady-state (13)C MFA to examine heterotrophic or mixotrophic growth of cyanobacteria, as well as recent studies that have pioneered the use of isotopically nonstationary MFA (INST-MFA) to study autotrophic cultures. We also provide recommendations for the design and analysis of INST-MFA experiments in cyanobacteria, based on our previous experience and a series of simulation studies used to assess the selection of measurements and sample time points. We anticipate that this emerging knowledgebase of prior (13)C MFA studies, optimized experimental protocols, and public software tools will catalyze increasing use of (13)C MFA techniques by the cyanobacteria research community.


An in situ measurement of extracellular cysteamine, homocysteine, and cysteine concentrations in organotypic hippocampal slice cultures by integration of electroosmotic sampling and microfluidic analysis.
We demonstrate an all-electric sampling/derivatization/separation/detection system for the quantitation of thiols in tissue cultures. Extracellular fluid collected from rat organotypic hippocampal slice cultures (OHSCs) by electroosmotic flow through an 11 cm (length) × 50 μm (i.d.) sampling capillary is introduced to a simple microfluidic chip for derivatization, continuous flow-gated injection, separation, and detection. With the help of a fluorogenic, thiol-specific reagent, ThioGlo-1, we have successfully separated and detected the extracellular levels of free reduced cysteamine, homocysteine, and cysteine from OHSCs within 25 s in a 23 mm separation channel with a confocal laser-induced fluorescence (LIF) detector. Attention to the conductivities of the fluids being transported is required for successful flow-gated injections. When the sample conductivity is much higher than the run buffer conductivities, the electroosmotic velocities are such that there is less fluid coming by electroosmosis into the cross from the sample/reagent channel than is leaving by electroosmosis into the separation and waste channels. The resulting decrease in the internal fluid pressure in the injection cross pulls flow from the gated channel. This process may completely shut down the gated injection. Using a glycylglycine buffer with physiological osmolarity but only 62% of physiological conductivity and augmenting the conductivity of the run buffers solved this problem. Quantitation is by standard additions. Concentrations of cysteamine, homocysteine, and cysteine in the extracellular space of OHSCs are 10.6 ± 1.0 nM (n = 70), 0.18 ± 0.01 μM (n = 53), and 11.1 ± 1.2 μM (n = 70), respectively. This is the first in situ quantitative estimation of endogenous cysteamine in brain tissue. Extracellular levels of homocysteine and cysteine are comparable with other reported values.


Anaesthesia for phaeochromocytoma resection: role of thoracic epidural blockade.
Two case reports are presented of patients who underwent surgical removal of phaeochromocytoma at Goroka Base Hospital, one with the use of thoracic epidural blockade supplemented with light general anaesthesia. This patient had a much smoother perioperative anaesthetic course than the other, with minimal elevation of blood pressure during the procedure. The paper highlights the value of epidural blockade for excision of phaeochromocytoma, especially in situations where the latest recommended methods and advanced monitoring facilities are unavailable.


[The scimitar syndrome in computed tomography and intravenous subtraction angiography].
A case of scimitar syndrome is reported in which the diagnosis was first suggested on chest radiograph. The diagnosis was confirmed by computed tomography (CT) and intravenous digital subtraction angiography (DSA). CT and DSA seem to be able to evaluate the structure and distortion of the lung and the vessels.


Does Encouragement by Others Increase Rape Reporting? Findings from a National Sample of Women.
Our study explores the role of victims' consultation with others about whether or not to report their rape to police. Three groups were observed within this sample of 435 rape victims from a national telephone household probability sample of women: those who did not consult with anyone about reporting (n = 364), those who consulted with someone and were encouraged to report to police (n = 40), and those who consulted with someone and were not encouraged to report (n = 31). Descriptive analyses indicated that the encouraged group was more likely to report to police than either of the other two groups (which did not differ from each other). Because there were no differences between the two consulting groups on demographic or rape-related variables, they were combined in subsequent analyses. Consulting with others about whether to report, peri-traumatic fear of injury or death, assault perpetration by a stranger, and concerns about contracting a sexually transmitted disease were significant predictors of reporting to police after controlling for other significant predictors in a multivariate regression analysis. Implications of these findings are discussed, including the benefits and consequences of formal rape reporting for victims, and the role that disclosure recipients may have in assisting victims post-rape (e.g., encouragement of reporting, emotional support).


Short telomeres: a novel potential predictor of relapse in Ewing sarcoma.
Despite advances in therapy, >50% of patients with Ewing sarcoma will relapse. The current prognostic factors are not optimal for risk prediction. Studies have shown that telomere length could predict outcome in different malignancies. Our aim was to evaluate whether telomere length could be a better prognostic factor in Ewing sarcoma and correlate the results with clinical variables, outcome, and chromosomal instability. Telomere length was determined in the primary tumor and peripheral blood of 32 patients with Ewing sarcoma. Chromosomal instability was evaluated by combining classical cytogenetics, comparative genomic hybridization and random aneuploidy. Telomere length was correlated to clinical variables, chromosomal instability, and outcome. In 75% of the tumors, changes in telomere length, when compared with the corresponding peripheral blood lymphocytes, were noted. The majority of changes consisted of a reduction in telomere length. Patients harboring shorter telomeres had a significantly adverse outcome (P = 0.015). Chromosomal instability was identified in 65% of tumors, significantly correlating with short telomeres (P = 0.0094). Using multivariate analysis, telomere length remained the only significant prognostic variable (P = 0.034). Patients with short telomeres had a 5.3-fold risk of relapse as compared to those with unchanged or longer telomeres. We have shown that tumors with telomere length reduction result in genomic instability. In addition, telomere length reduction was the only significant predictor of outcome. We suggest that reduction of telomere length in tumor cells at diagnosis could serve as a prognostic marker in Ewing sarcoma.


Acute promonocytic leukemia with ocular involvement.
A 3-month-old male infant had bilateral redness of the eyes. Large, immature blast cells were noted in material obtained by anterior chamber tap, and the diagnosis of acute promonocytic leukemia was confirmed by bone marrow aspiration and autopsy. Detailed clinical, histopathological, histochemical, and electron microscopic studies were carried out. The case showed forcibly that children with sterile hypopyon should be investigated for malignancy.


Health-related quality of life in inflammatory bowel disease measured with the generic 15D instrument.
In many surveys, inflammatory bowel disease (IBD) has been shown to have a negative impact on health-related quality of life (HRQoL), especially when the disease is active. The purpose of this study was to compare a disease-specific HRQoL tool (Inflammatory Bowel Disease Questionnaire, IBDQ) and a generic HRQoL tool (15D) in a large cohort of IBD patients, to assess the ability of the 15D to detect differences in HRQoL between disease states and to compare the HRQoL of IBD patients with that of the general population. The study population comprised 2,931 IBD patients over 18 picked from a national Social Insurance Institute register and from a patient organization register. The 15D data for the general population came from the National Health 2000 Health Examination Survey. For patients with IBD, the 15D tool was feasible and had good discriminatory power. The total 15D score was significantly higher among patients with less active disease estimated by frequency of IBD symptoms and was strongly correlated with total IBDQ score. The general population scored significantly higher than did the study subjects on most of the 15D dimensions. The 15D was a fast and easy-to-apply method for the examination of HRQoL in IBD patients. In addition to HRQoL studies it could be used in everyday practice as well. Patients with IBD have worse HRQoL than do gender- and age-standardized controls.


Chinese-Australian women's beliefs about cancer: implications for health promotion.
Ethnicity and culture play significant roles in determining how an individual is likely to understand and explain cancer, which, in turn, is posited to have an impact on cancer screening behavior. Chinese women in Western countries are consistently reported to have low participation rates in mammographic screening. This may be related to the fact that women of Chinese ancestry have different images and beliefs about cancer, which can have implications for participation in health promotion programs regarding cancer prevention and early detection. To investigate this issue, a qualitative study involving in-depth interviews with 20 Chinese-Australian women was conducted. Embedded in the women's images of cancer were notions associated with fear, mystery, contagion, and stigma. Based on information provided by the women who participated in this study, 6 domains of folk explanations about the causes of cancer were identified: lifestyle, stress, environment, genes, unknown causes, and destiny. These beliefs should be considered in the design of breast health promotion programs because they are likely to have a bearing on Chinese-Australian women's attitudes regarding the value they perceive of cancer screening.


How Does CEO's Environmental Awareness Affect Technological Innovation?
In this paper, we conduct an empirical study on the impact of CEOs' environmental awareness on technological innovation. To this end, we obtain a large sample with 7615 observations from Chinese A-share listed firms between the years of 2003 and 2014. Our empirical results show that a CEO's environmental awareness has a significant positive impact on technological innovation of his/her enterprise. Environmentally conscious CEOs will invest more in R&D and obtain more patents. This will help their enterprises achieve higher efficiency of technological innovation. Furthermore, the environmental awareness of a CEO has a more significant impact on technological innovation if his/her enterprise is subject to a higher level of monitoring. We also conduct robustness check of our findings and provide managerial insights and proactive government policies to raise the environmental awareness of CEOs and improve the innovation vitality of enterprises.


Antioxidant and anti-atherosclerotic potential of Banana (Musa spp): A review of biological mechanisms for prevention and protection against atherosclerosis.
To review the antioxidant and anti-atherosclerotic potential of whole banana, banana flour, and its bioactive compounds. A non-systematic review of the literature covering the past 20 years, using the following databases and searching bases: PUBMED/MEDLINE: https://www.ncbi.nlm.nih.gov/pubmed/; Google Scholar: https://scholar.google.com.br/; and "Literatura Latinoamericana em Ciências da Saúde"/Latin American Literature in Life Sciences [LILACS]: http://lilacs.bvsalud.org/, was done. Studies with incomplete methodology and design were excluded. Bananas from different species are a good source of carbohydrates, dietary fiber, proteins, polyunsaturated fatty acids, potassium, carotenoids, flavonoids, vitamin C and E, phytosterols, gallocatechin, catechin, and other polyphenols. Some of these compounds play trigger important biological roles as antioxidants or anti-atherosclerotic and cardiovascular protective substances. This review summarizes and explains thirteen protective biological mechanisms of banana bioactive compounds and banana products. Including banana and its products in dietary menus, in food products and nutraceuticals should improve cardiovascular health of the populations.


Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males.
The appetite-suppressing potential of liver-expressed antimicrobial peptide 2 (LEAP2), and its antagonistic effects on the hunger-inducing hormone ghrelin have attracted scientific interest. It is unclear how LEAP2 is influenced by fasting and how it responds to specific nutrients. The purpose of this investigation was to assess whether LEAP2 concentration 1) decreases after fasting, 2) increases postprandially, and 3) is regulated by nutrient sensing in the splanchnic bed. Plasma LEAP2 concentration was measured in blood samples from 5 clinical cross-over trials, following 1) 36 h of fasting (n = 8), 2) 10 h of fasting (n = 37, baseline data pooled from 4 of the clinical trials), 3) Oral and intravenous glucose administration (n = 11), 4) Oral and intravenous Na-lactate administration (n = 10), and 5) Oral and intravenous Na-β-hydroxybutyrate (BHB) administration (n = 8). All 5 trials included healthy males. Compared with a 10-h fasting period, the median LEAP2 concentration was 38% lower following 36 h of fasting (P < 0.001). Oral administration of glucose elevated, whereas intravenous glucose administration lowered LEAP2 concentration (intervention x time, P = 0.001), resulting in a mean difference of 9 ng/mL (95% confidence interval [CI]: 1, 17) after 120 min. Oral lactate increased, and intravenous lactate decreased LEAP2 (intervention x time, P = 0.007), with a mean difference between interventions of 10 ng/mL (95% CI: 6, 15) after 120 min. In contrast, oral and intravenous administration of BHB reduced the LEAP2 concentration (main effect of time, P < 0.001). Our investigations show that LEAP2 concentration was lower after a 36-h fast than an overnight fast and that oral delivery of glucose and lactate elevated LEAP2 concentration compared with intravenous administration, whereas LEAP2 concentrations decreased with both oral and intravenous BHB. This indicates that the LEAP2 concentration is sensitive to intestinal exposure to specific substrates, highlighting the need for future studies exploring the relationship between nutrients and LEAP2. This trial was registered at clinicaltrials.gov as NCT01840098, NCT03204877, NCT04299815, NCT03935841, and NCT01705782.


Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes.
Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has remained unresolved. Here we used concurrent transcriptome-wide identification of NMD substrates and their 5'-3' decay intermediates to establish that SMG6-catalyzed endonucleolysis widely initiates the degradation of human nonsense RNAs, whereas decapping is used to a lesser extent. We also show that a large proportion of genes hosting snoRNAs in their introns produce considerable amounts of NMD-sensitive splice variants, indicating that these RNAs are merely by-products of a primary snoRNA production process. Additionally, transcripts from genes encoding multiple snoRNAs often yield alternative transcript isoforms that allow for differential expression of individual coencoded snoRNAs. Based on our findings, we hypothesize that snoRNA host genes need to be highly transcribed to accommodate high levels of snoRNA production and that the expression of individual snoRNAs and their cognate spliced RNA can be uncoupled via alternative splicing and NMD.


Heart failure with a normal left ventricular ejection fraction: diastolic heart failure.
A reduced left ventricular ejection fraction measured by echocardiography in a patient with clinical features of heart failure demonstrates that the patient has a cardiac abnormality and that the clinical picture is, in fact, due to heart failure. As such, a reduced ejection fraction (< 0.30 or 0.35) has been used as entry criteria for almost all the large clinical trials that guide our therapy of patients with heart failure. However, it has been recently recognized that a substantial and increasing proportion of patients with heart failure have a normal ejection fraction (> 0.50). Such patients are typically elderly women with systolic hypertension. These patients are subject to the sudden development of pulmonary congestion (flash pulmonary edema). The finding of heart failure in patients with a normal ejection fraction has focused attention on the role of diastolic dysfunction in producing symptomatic heart failure. The optimal treatment of patients with heart failure and normal ejection fraction has not yet been defined, but the control of systolic hypertension and the avoidance of fluid overload are important.


Validation of Michigan neuropathy screening instrument for diabetic peripheral neuropathy.
The reliability and accuracy of the Michigan neuropathy screening instrument (MNSI) have been discussed recently. As a result of the difficulties of performing and analyzing nerve biopsy as a standard diagnostic test, electromyography and neuronography is used as the best alternative diagnostic procedure. The objective of this study was to determine the diagnostic performance of the test characteristics and cut-off point of MNSI scoring for the diagnosis of diabetic peripheral neuropathy. Over a 2-year period, a cross-sectional study was conducted on 176 type 2 diabetic patients. An internist carried out the MNSI and the sum of scores varying from 0 to 1 for each abnormality as revealed in foot appearance, ulceration, ankle reflexes and vibratory perception has been recorded. A neurologist, who was blind to the MNSI scores, performed all neurophysiological studies. The test performance characteristics of the MNSI procedure were measured for different cut-off values. MNSI scores of 1.5, 2.0, 2.5 and 3.0 were assessed as cut-off values. Sensitivities were 79%, 65%, 50% and 35% and specificities were 65%, 83%, 91% and 94%, respectively. Positive predictive values increased and negative predictive values decreased for each score. Accuracies, likelihood ratios and post-test probabilities were measured. The accuracy of MNSI scoring makes it a useful screening test for diabetic neuropathy in taking a decision regarding which patients should be referred to a neurologist for electrophysiological studies. High specificity, likelihood ratios over 5 and a moderate to good post-test probability give a high diagnostic impact for MNSI scoring. We suggest a cut-off point of 2 for the MNSI procedure. However, electrophysiological studies should be considered when the patient has signs and symptoms other than those rated by the MNSI, suggesting peripheral nerve involvement, and also because the MNSI is still just a screening test.


Review article: a practical approach to the clinical management of NSAID enteropathy.
Co-prescription of acid suppressive therapy, together with advances in small bowel imaging techniques, have shifted the burden of NSAID-related toxicity from gastro-duodenal to more distal small bowel injury. Due to predominantly subclinical disease, NSAID enteropathy remains under-recognised, with an incidence of 53-80% amongst healthy short-term users, and a prevalence of 50-71% following long-term (>3 months) use. Despite their distinct pathogenesis, those at risk of NSAID-related gastro-duodenal and small bowel complications share several risk factors. Clinical complications of NSAID enteropathy such as protein-losing enteropathy, small bowel strictures and diaphragm disease, confer significant morbidity, and are often irreversible. Small bowel prophylaxis has proven of modest efficacy after short-term, high-dose NSAID use in asymptomatic patients. While selective COX-2 inhibitors are associated with fewer gastro-duodenal complications relative to non-selective NSAIDs, their comparative benefit in protecting against small bowel enteropathy remains unclear. Prophylaxis should be considered in those at high risk of small bowel complications, as treatment options for established disease remain limited; however, the optimal agent remains unclear. We propose a clinical algorithm that may help prevent, monitor, investigate, and manage the sequelae of NSAID-induced small bowel toxicity.


Psychopathology of childhood.
We considered problems of assessment and taxonomy that have hindered the study of childhood disorders. Many instruments have been developed for assessing children's behavior as seen by parents, teachers, clinicians, trained observers, peers, and children themselves. Multivariate analyses of behavior problems show consistencies in the identification of a few broad-band patterns and more numerous narrow-band syndromes, despite differences in specific items comprising different instruments. Satisfactory reliability has been achieved in many instances, although the variability of children's problem behavior limits agreement among informants who see children under different conditions. Despite their disagreements, however, each informant's perspective may validly contribute to the comprehensive assessment of a child's needs. The quantitative, relativistic, and developmental aspects of children's behavior disorders argue for replacing categorical approaches to assessment and taxonomy with taxometric approaches that capitalize on quantitative methods for identifying and assessing children's behavioral problems and competencies.


Nanothin ferrocene film plasma polymerized over physisorbed glucose oxidase: high-throughput fabrication of bioelectronic devices without chemical modifications.
We describe a method for creating a mediator-containing interface between an enzyme and an electrode, achieving simpler and more reliable immobilization of the enzyme with the enhanced detection sensitivity. A nanothin polymer film containing a redox mediator, made of dimethylaminomethylferrocene, was plasma-deposited directly onto a glucose oxidase-physisorbed electrode, with which a relevant bioelectrochemical signal was observed without prior or further chemical modification of the enzyme molecules. The results of the surface characterizations before and after the enzyme immobilization showed that this method gave control over the spatial orientation of single enzyme molecules in favor of efficient and reproducible signal generation. Considering that the film deposition was performed using microfabrication-compatible organic plasma, our new method has a great potential of enabling high-throughput production of bioelectronic devices without chemical modification steps.


3D-Printed, Portable, Fluorescent-Sensing Platform for Smartphone-Capable Detection of Organophosphorus Residue Using Reaction-Based Aggregation Induced Emission Luminogens.
Development of an easy-to-use, low-cost, household device can help the consumer quickly identify an organophosphorus (OP) residue concentration level. In this work, we demonstrate a 3D-printed, portable, fluorescent-sensing platform for smartphone-capable detection of OPs in vegetables. For development of the proposed device, we utilize the smartphone for capturing the strong thiol-activated fluorescence, which was produced by hydrolysis of OPs in the presence of alkali. The thiol-responsive AIEgen (maleimide-functionalized tetraphenylethylene) was non-emissive in both solution and the solid state but could be readily lighted up by the click addition of thiol to its MI pendant. An android application "Detection" has been developed on the basis of the gray value to analyze the different concentration levels of OPs in vegetable samples. The gray value was linearly related with the concentration of five kinds of organophosphorus residue, ranging from 0 to 20 μg/mL. It was also applied for determination of OPs residue in the leaves of cowpea, celery, and Chinese cabbage. Different from acetylcholinesterase enzyme-based sensors for poor stability under high temperature, the proposed method was a direct detection method for OPs and can be used for rapid monitoring of OPs residue concentration levels before LC-MS analysis.


Discussing breast cancer risk in primary care.
Options for managing breast cancer risk now include screening, genetic testing, lifestyle modification, medication, and surgery. A woman's knowledge of her risk factors for breast cancer, her perceptions of that risk, and her concerns about cancer all shape her decisions about cancer screening and prevention. Physicians should involve women patients in making informed screening decisions, while reviewing their health risks and the benefits and risks associated with different courses of action. All women should be involved in this process, with special attention to older socioeconomically disadvantaged women, who are frequently left out of such discussions. Physicians can play a major role in reducing cancer disparities and the corresponding rates of breast cancer morbidity and mortality by keeping current in their knowledge of risk assessment, broadening the range of patients with whom they communicate about risk, and enhancing their communication skills to address diverse patient needs.


Improving the Hsp90 Inhibitors Containing 4-(2,4-Dihydroxyphenyl)-1,2,3-thiadiazole Scaffold: Synthesis, Affinity and Effect on Cancer Cells.
Human Hsp90 chaperone inhibitors are known to be potential anticancer drugs. Previously we have shown a couple of 5-aryl-4-(2,4-dihydroxyphenyl)-1,2,3-thiadiazoles to be promising anticancer agents. To improve the compounds containing 4-(2,4-dihydroxyphenyl)-1,2,3-thiadiazole scaffold as human Hsp90 inhibitors. We employed chemical synthesis to obtain new compounds and assayed their binding to Hsp90 using the fluorescence thermal shift assay and used MTT assays to determine their effect on cancer cells. A series of compounds containing the 4-(2,4-dihydroxyphenyl)-1,2,3-thiadiazole scaffold were synthesized as Hsp90 inhibitors. Analysis of their binding to the recombinant N-terminal domain of Hsp90 revealed that four of these compounds bound to Hsp90 with Kd of 0.6 to 0.8 nM. The compounds fully inhibited the growth of all tested cancer cell lines: A549 (lung adenocarcinoma), IGR39 (melanoma), and U87 (glioblastoma), with the effective antiproliferative concentration (EC50) of the compounds reaching 0.35 µM. This series of 14 novel and efficient Hsp90 inhibitors provided additional information on the structure-activity relationship of Hsp90 inhibitors and may be further developed into drugs targeting Hsp90.


Validation of the Strengths and Difficulties Questionnaire (SDQ) emotional subscale in assessing depression and anxiety across development.
Emotional disorders are common in childhood, and their prevalence sharply increases during adolescence. The Strengths and Difficulties Questionnaire (SDQ) is widely used for screening emotional and behavioural difficulties in children and young people, but little is known about the accuracy of the emotional subscale (SDQ-E) in detecting emotional disorders, and whether this changes over development. Such knowledge is important in determining whether symptom changes across age are due to developmental or measurement differences. This study assessed the validity of the SDQ-E and two individual items (low mood and general worry) in differentiating between cases and non-cases of Major Depressive Disorder (MDD), Generalised Anxiety Disorder (GAD), and other anxiety disorders across ages 7, 10, 13, 15, and 25 years in a UK population cohort. Analyses showed moderate accuracy of the subscale in discriminating cases of MDD (AUC = 0.67-0.85), and high accuracy for discriminating cases of GAD (AUC = 0.80-0.93) and any anxiety disorder (AUC = 0.74-0.83) compared to non-cases. The SDQ-E performed well across ages and sex, and generally performed better than the two individual items. Together our findings validate the SDQ-E as a screen for emotional disorders during childhood, adolescence, and early adulthood, and as a tool for longitudinal research on depression and anxiety disorders.


Universal Unitary Transfer of Continuous-Variable Quantum States into a Few Qubits.
We present a protocol for transferring arbitrary continuous-variable quantum states into a few discrete-variable qubits and back. The protocol is deterministic and utilizes only two-mode Rabi-type interactions that are readily available in trapped-ion and superconducting circuit platforms. The inevitable errors caused by transferring an infinite-dimensional state into a finite-dimensional register are suppressed exponentially with the number of qubits. Furthermore, the encoded states exhibit robustness against noise, such as dephasing and amplitude damping, acting on the qubits. Our protocol thus provides a powerful and flexible tool for discrete-continuous hybrid quantum systems.


Glutamate-immunoreactivity in the trigeminal and dorsal root ganglia, and intraspinal neurons and fibres in the dorsal horn of the rat.
Putative aspartergic and glutamatergic sensory neurons in the rat were identified by autoradiography and immunocytochemistry respectively. Approximately 3% of large L4 dorsal root ganglion neurons (diameter 18-52 microns) accumulated radiolabelled aspartate, whereas all satellite glia had high affinity for the amino acid. Glutamate-immunofluorescent (Glu-FITC) dorsal root ganglia neurons comprised 38.3% at S1, 35.6% at L2, 33.9% at C5 and 28.8% at T6. Numbers of immunoreactive neurons were higher with the more sensitive peroxidase-anti-peroxidase (Glu-PAP) method; and the cell counts totalled 42% (S1), 41.2% (L4), 35% (C5) and 34.6% (T6). The trigeminal ganglion (TG) contained 24% Glu-FITC and 32.3% Glu-PAP positive cells. The majority of glutamate-immunoreactive sensory neurons were small, ranging from 10-35 microns with median diameters of 17.5 microns (C5), 21 microns (S1), 24.2 microns (TG) and 28.5 microns (L2). It is evident therefore, that a subgroup of class B cells are glutamatergic. Glutamate immunoreactivity in the spinal cord was similar in all segments and was localized in the superficial lamina and substantia gelatinosa of the dorsal horn. Stained interneurons were located among the immunoreactive fibres. The dorsolateral funiculus contained dense plexus of immunoreactive fibres which increased in prominence after intraperitoneal injection of L-gluatamate, but penetration of exogenous glutamate into the grey matter was limited. Instead, the meninges and basal layers of the spinal blood vessels were intensely immunoreactive. The studies describe the subtypes of acidic amino acidergic neurons and relates the immunohistochemistry to a functional subclass.


Protein disorder-to-order transition enhances the nucleosome-binding affinity of H1.
Intrinsically disordered proteins are crucial elements of chromatin heterogenous organization. While disorder in the histone tails enables a large variation of inter-nucleosome arrangements, disorder within the chromatin-binding proteins facilitates promiscuous binding to a wide range of different molecular targets, consistent with structural heterogeneity. Among the partially disordered chromatin-binding proteins, the H1 linker histone influences a myriad of chromatin characteristics including compaction, nucleosome spacing, transcription regulation, and the recruitment of other chromatin regulating proteins. Although it is now established that the long C-terminal domain (CTD) of H1 remains disordered upon nucleosome binding and that such disorder favours chromatin fluidity, the structural behaviour and thereby the role/function of the N-terminal domain (NTD) within chromatin is yet unresolved. On the basis of microsecond-long parallel-tempering metadynamics and temperature-replica exchange atomistic molecular dynamics simulations of different H1 NTD subtypes, we demonstrate that the NTD is completely unstructured in solution but undergoes an important disorder-to-order transition upon nucleosome binding: it forms a helix that enhances its DNA binding ability. Further, we show that the helical propensity of the H1 NTD is subtype-dependent and correlates with the experimentally observed binding affinity of H1 subtypes, suggesting an important functional implication of this disorder-to-order transition.


Acute medical conditions in under five year old children at a public hospital in Kenya.
To determine the prevalence of childhood preventable and treatable medical conditions and the parent's/guardian's knowledge about the conditions and their management. A descriptive cross-sectional study. Paediatric medical wards at Kenyatta National hospital All children aged 0-60 months with preventable conditions (that included pneumonia, malaria, diarrhoea/dehydration, meningitis and malnutrition) in paediatric wards who had stayed in the ward for 24 to 48 hours. Two hundred and fifty six parents/guardians staying with their children were recruited into the study. The vast majority (85.5%) of the children were aged less than two years. The prevalence of the acute treatable and preventable medical conditions was 88.6% over a one month period. The leading cause of admission for most children was pneumonia (31.6%) followed by malnutrition (16.8%) and gastro-enteritis (16%). Other conditions included neonatal sepsis (9.1%), measles (6%) and malaria (4.8%). The parents'/guardians' mean and median age was 26 years and the majority (89.8%) were mothers. A great proportion (46.5%) of the parents/guardians had attained at least some primary education. More than 70% of the parents/guardians were found to lack knowledge about their children's health problems and the drugs they were using. This was regardless of the parent's/guardians level of education and the frequency of admission of the child. Acute preventable and treatable medical conditions at KNH are highly prevalent, and the leading conditions include pneumonia, malnutrition and gastroenteritis. Most parents/guardians did not understand their children's health problems regardless of their level of education.


[Venous thromboembolic disease: which coagulation screening, for whom, when?].
Testing for laboratory evidence of thrombophilia is now common but it has limited predictive value for the majority of unselected symptomatic patients. So when is testing indicated ? And which one? The term "thrombophilia" describes disorders of the haemostatic mechanisms which are likely to predispose to thrombosis. Thrombophilia may be heritable, acquired or mixed, resulting of the environment interacting with genetic background. To date, a limited number of genetic variants and other defects are proven to be independent risk factors for venous thromboembolism. These include antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden, the prothrombin gene mutation, hyperhomocysteinemia and antiphospholipid antibodies. There is no good evidence currently available to support the hypothesis that heritable thrombophilias increase the risk of arterial disease. But acquired or mixed thrombophilias such as hyperhomocysteinemia and antiphospholipid antibodies have been found in association with both venous and arterial thrombotic disorders. When testing for thrombophilia is indicated, especially in case of venous thromboembolism, it should include assays for heritable, mixed or acquired defects: deficiency of antithrombin, protein C or protein S, factor V Leiden and prothrombin G20210A mutations, elevated factor VIII, hyperhomocysteinemia and for antiphospholipid antibodies. Depending on the site of venous thrombosis, laboratory testing to exclude myeloproliferative disorders should be performed.


Compound leaves are associated with high hydraulic conductance and photosynthetic capacity: evidence from trees in Northeast China.
Characterizing differences in key functional traits between simple-leaved (SL) and compound-leaved (CL) tree species can contribute to a better understanding of the adaptive significance of compound leaf form. In particular, this information may provide a mechanistic explanation to the long-proposed fast-growth hypothesis of CL tree species. Here, using five SL and five CL tree species co-occurring in a typical temperate forest of Northeast China, we tested whether higher hydraulic efficiency underlies potentially high photosynthetic capacity in CL species. We found that the CL species had significantly higher hydraulic conductance at the whole-branch level than the SL species (0.52 ± 0.13 vs 0.15 ± 0.04 × 10-4 kg m-2 s-1 Pa-1, P = 0.029). No significant difference in net photosynthetic rate (14.7 ± 2.43 vs 12.5 ± 2.05 μmol m-2 s-1, P = 0.511) was detected between these two groups, but this was largely due to the existence of one outlier species in each of the two functional groups. Scrutinization of the intragroup variations in functional traits revealed that distinctions of the two outlier species in wood type (ring- vs diffuse-porous) from their respective functional groups have likely contributed to their aberrant physiological performances. The potentially high photosynthetic capacity of CL species seems to require ring-porous wood to achieve high hydraulic efficiency. Due to its limitation on leaf photosynthetic capacity, diffuse-porous wood with lower hydraulic conductivity largely precludes its combination with the 'throw-away' strategy (i.e., annually replacing the stem-like rachises) of compound-leaved tree species, which intrinsically requires high carbon assimilation rate to compensate for their extra carbon losses. Our results for the first time show clear differentiation in hydraulic architecture and CO2 assimilation between sympatric SL and CL species, which contributes to the probing of the underlying mechanism responsible for the potential fast growth of trees with compound leaves.


Complement Gene Variants and Shiga Toxin-Producing Escherichia coli-Associated Hemolytic Uremic Syndrome: Retrospective Genetic and Clinical Study.
Inherited complement hyperactivation is critical for the pathogenesis of atypical hemolytic uremic syndrome (HUS) but undetermined in postdiarrheal HUS. Our aim was to investigate complement activation and variants of complement genes, and their association with disease severity in children with Shiga toxin-associated HUS. Determination of complement biomarkers levels and next-generation sequencing for the six susceptibility genes for atypical HUS were performed in 108 children with a clinical diagnosis of post-diarrheal HUS (75 Shiga toxin-positive, and 33 Shiga toxin-negative) and 80 French controls. As an independent control cohort, we analyzed the genotypes in 503 European individuals from the 1000 Genomes Project. During the acute phase of HUS, plasma levels of C3 and sC5b-9 were increased, and half of patients had decreased membrane cofactor protein expression, which normalized after 2 weeks. Variants with minor allele frequency <1% were identified in 12 Shiga toxin-positive patients with HUS (12 out of 75, 16%), including pathogenic variants in four (four out of 75, 5%), with no significant differences compared with Shiga toxin-negative patients with HUS and controls. Pathogenic variants with minor allele frequency <0.1% were found in three Shiga toxin-positive patients with HUS (three out of 75, 4%) versus only four European controls (four out of 503, 0.8%) (odds ratio, 5.2; 95% confidence interval, 1.1 to 24; P=0.03). The genetic background did not significantly affect dialysis requirement, neurologic manifestations, and sC5b-9 level during the acute phase, and incident CKD during follow-up. However, the only patient who progressed to ESKD within 3 years carried a factor H pathogenic variant. Rare variants and complement activation biomarkers were not associated with severity of Shiga toxin-associated HUS. Only pathogenic variants with minor allele frequency <0.1% are more frequent in Shiga toxin-positive patients with HUS than in controls.


The interaction of antiarrhythmics with an anionic receptor site.
The applications of the methods of computational chemistry to the study of various physiochemical properties (molecular conformation, molecular electrostatic potentials, basicity, reactivity, lipophilicity) of antiarrhythmics are reviewed. The focus is on the application of ab initio SCF quantum mechanical methods to antiarrhythmic-receptor interactions and proton transfer, including the effect of small cations and water.


Sulfate anion helices formed by the assistance of a flip-flop water chain.
A flip-flop extended water structure assists the formation of sulfate anion helices (both left- and right-handed) in a crystalline hydrate of a simple organic-inorganic compound [C6H10N2]SO4. 1.5H2O (1).


[Hemato-tissue eosinophilia in a case of ulcerative rectocolitis].
A case of ulcerous rectocolitis presenting a remarkable haematic and tissue eosinophilia, both rectal and gastric, is described. After therapy, the eosinphil complement decreased in the blood but not in the colic mucosa. It is suggested that eosinphilia is not a particular characteristic of ulcerous colitis, but the expression of an inidvidual reaction to an inflammatory stimulus.


A method for exposing the internal anatomy of small and delicate tissues for correlated SEM/TEM studies using polyethylene glycol embedding.
A method for preparing and handling large, clean, distortion-free cut surfaces through small and delicate tissues for correlated SEM/TEM examination is described. In this method, tissues are fixed according to conventional protocols; however, instead of critical-point-drying after fixation, tissues are first embedded in polyethylene glycol (PEG), a water-soluble waxy solid. Tissue blocks are easily oriented and sectioned to the desired regions, immersed in a solvent to remove PEG, critical-point-dried, and examined with an SEM. The same tissue blocks can be reworked for TEM by immersing in propylene oxide and embedding in an epoxy resin.


Replication study of the vitamin D receptor (VDR) genotype association with skeletal muscle traits and sarcopenia.
Polymorphisms in the vitamin D receptor (VDR) gene are some of the most studied in relation to skeletal muscle traits and significant associations have been observed by multiple groups. One such paper by our group provided the first evidence of a genetic association with sarcopenia in men, but that finding has yet to be replicated in an independent cohort. In the present study, we examined multiple VDR polymorphisms in relation to skeletal muscle traits and sarcopenia in 864 men and women across the adult age span. In addition to VDR genotypes and haplotypes, measurements of skeletal muscle strength and fat-free mass (FFM) were determined in all subjects and a measure of sarcopenia was calculated. We observed significant associations between Fok1 and Bsm1 genotypes and skeletal muscle strength in men and women, though these associations were modest and no significant associations were observed for these polymorphisms and muscle mass traits nor for Bsm1-Taq1 haplotype with muscle strength. Fok1 FF genotype was associated with an increased the risk of sarcopenia in older women compared to f-allele carriers (1.3-fold higher risk). These results support previous findings that VDR genetic variation appears to impact skeletal muscle strength and risk for sarcopenia but the influence is modest.


Simultaneous determination of cannabidiol, cannabinol, and delta9-tetrahydrocannabinol in human hair by gas chromatography-mass spectrometry.
An analytical method was developed for evaluating the cannabidiol (CBD), cannabinol (CBN), and delta9-tetrahydrocannabinol (delta9-THC) level in human hair using gas chromatography-mass spectrometry (GC-MS). Hair samples (50 mg) were washed with isopropyl alcohol and cut into small fragments (< 1 mm). After adding a deuterated internal standard, the hair samples were incubated in 1.0 M NaOH for 10 min at 95 degrees C. The analytes from the resulting hydrolyzed samples were extracted using a mixture of n-hexane-ethyl acetate (75:25, v/v). The extracts were then evaporated, derivatized, and injected into the GC-MS. The recovery ranges of CBD, CBN, and delta9-THC at three concentration levels were 37.9-94.5% with good correlation coefficients (r2 >0.9989). The intra-day precision and accuracy ranged from -9.4% to 17.7%, and the inter-day precision and accuracy ranged from -15.5% to 14.5%, respectively. The limits of detection (LOD) for CBD, CBN, and delta9-THC were 0.005, 0.002, and 0.006 ng/mg, respectively. The applicability of this method of analyzing the hair samples from cannabis abusers was demonstrated.


Full recovery of near complete tear of anterior cruciate ligament without surgery: a case report.
The anterior cruciate ligament (ACL) is the region where spraining or tearing is most prevalent when the knee is injured. Complete ACL ruptures have a much less favorable outcome without surgical intervention. Polydeoxyribonucleotide (PDRN) is a relatively safe substance widely used for regenerative therapy. A 43-year-old female patient visited our clinic with Rt. knee pain after slipping, which she rated as 7/10 on a numeric rating scale. She was diagnosed as having a near complete tear of the ACL at the femoral attachment, partial tear of the lateral collateral ligament. Ultrasound-guided PDRN injections were carried out 5 times at intervals of about 2 weeks. At 3-month follow-up, the patient demonstrated an improvement in knee symptoms (numeric rating scale 0) and ROM without any complications. Even after 2 years and 5 months since the diagnosis, she has been doing her daily life well without any pain. This is the first report of successful PDRN injection for near complete tear of ACL and partial tear of lateral collateral ligament without surgery.


The new role of physical therapy in home care.
As the country's efforts to provide healthcare to the elderly shifts from facility-based to home-based care, physical therapy in the home has continued to grow as both an effective treatment modality and a focus of home health payers. This article explores the unique advantages, limitations, and challenges of physical therapy rehabilitation in the home setting.


Moderately increased risks of Down's syndrome (1/51-1/270) identified on first trimester sequential screening: what do patients do with this information?
To document patient decisions after being informed of a first trimester sequential screen Down's syndrome risk between 1/51 and 1/270. A database analysis of sequential screen results for patients seen in the Philadelphia, PA (USA) area between January 2006 and March 2008 was examined. All patients with first trimester sequential screen Down's syndrome risks in the 1/51-1/270 range were identified. Patient decisions regarding invasive testing (prior to completing the second trimester stage of the sequential screen), completion of the second trimester blood draw or no additional testing were tabulated. A total of 10,850 patients underwent first trimester sequential screening during this interval. Five hundred and fifty-seven patients (5.1%) met the study inclusion criteria and had risks between 1/51 and 1/270. Ninety-three percent of these patients completed the sequential screening process before making any decisions regarding invasive testing. Four percent did not elect an invasive prenatal diagnosis procedure, but also did not complete the second trimester sequential screening blood draw and only 3.2% elected an invasive procedure based on their first trimester risk without completing the second trimester blood draw. Five women (0.9%) with low risks after the second stage screen chose to have an amniocentesis. The vast majority (97%) of patients in the moderately increased Down's syndrome risk range (1/51-1/270) following first trimester sequential screening did not pursue an invasive procedure based on their first trimester sequential screen risk. Using a > or = 1/50 risk cut-off in the first trimester is an effective screening policy for sequential screening.


Health care access in three nations: Canada, insured America, and uninsured America.
This analysis provides new statistics for one of the oldest and fiercest debates in American health policy: whose residents have better access to health care, the United States' or Canada's? Data from the 2002-2003 Joint Canada U.S. Survey of Health show that, despite major differences in their health systems, most Canadians and Americans get the care they need. However, one group of Americans is much more likely to report serious access barriers--the uninsured. About one-third of currently or recently uninsured Americans, aged 18 to 64, said they could not get needed health care (over three times the rate of insured Americans or Canadians). Compared with Canadians and insured Americans, the uninsured are less likely to use hospital or physician services, and those who do are less satisfied with the care they receive. They are also less likely to purchase prescribed medications, due to cost. From a consumer perspective, the most salient feature of the Canadian system is its universality. In contrast, insured Americans under age 65 are at risk of losing their insurance and facing substantial access barriers.


Use of a customized 3D-printed external splint for the correction of a severe pectus excavatum in a 3-month-old kitten.
Pectus excavatum is a rare congenital or developmental deformity of the chest wall that has been reported in both dogs and cats. The clinical symptoms vary in severity and are correlated with the grade of the deformity. The most severe cases are at a very high risk of intra- and post-operative complications that could be fatal. A 3-month-old kitten was presented for severe dyspnea and exercise intolerance. After the radiographic diagnosis of severe pectus excavatum, a splint was designed based on the computed tomography scan of the kitten. A locking mechanism was applied on a dedicated pocket on the splint and secured with commercial glue. Five sutures were placed, the most caudal three with a surgical approach to the corresponding sternebra. The three caudal traction sutures were progressively tensioned during the first 2 weeks, and then tied. The splint was removed 1 month postoperatively; neither surgical nor splint-associated complications were observed. The kitten well tolerated the splint and the owner reported no further episodes of dyspnea or exercise intolerance. Vertebral and frontosagittal indexes were 3.2 and 9.1 at presentation, respectively, and 10.2 and 2.0 at 4 months postoperatively. The use of a patient-specific 3D-printed external splint associated with a progressive correction of the pectus excavatum can be a better solution for the treatment of severe cases of pectus excavatum, where a sudden distension of the rib cage could cause re-expansion injuries.


Intraocular pressure in American Bullfrogs (Rana catesbeiana) measured with rebound and applanation tonometry.
To measure the intraocular pressure (IOP) in normal American Bullfrogs (Rana catesbeiana) with rebound and applanation tonometry and to create calibration curves for both tonometers to determine the actual IOP of bullfrogs. Twenty bullfrogs were evaluated with slip-lamp biomicroscopy, indirect ophthalmoscopy, rebound tonometry, and applanation tonometry. Axial globe length and corneal thickness were measured in the three largest and the three smallest frogs with ultrasonography and optical coherence tomography, respectively. Two frogs were euthanized for direct manometry. The median IOP was 4 mmHg with the rebound tonometer and 16 mmHg with the applanation tonometer. The correlation coefficient (r2 ) between the manometry measurements and the tonometers was 0.95 and 0.91 for the rebound and applanation tonometers, respectively. The corresponding equations were y = 0.331x + 0.558 for the rebound tonometer and y = 0.675x + 1.907 for the applanation tonometer. The median axial globe length was 0.94 cm. The median corneal thickness was 0.093 mm. The rebound tonometer is the preferable tonometer for American Bullfrogs. Neither tonometer produced IOP readings that matched the manometer. The rebound tonometer was more precise and it was faster and easier to use.


Variations in sleep hygiene practices of women with and without insomnia.
Sleep hygiene education is a basic component of behavioral treatment for chronic insomnia, yet the actual sleep hygiene practices of people with insomnia have not been well documented. In this descriptive secondary analysis, midlife women ages 41-55 years with either chronic insomnia (n = 92) or good sleep (n = 29) kept diaries of sleep perceptions and sleep hygiene practices during 6 nights of somnographic monitoring at home. In both groups few reported smoking cigarettes (<10%), most drank caffeine (>80%), and many averaged 30 min of exercise per day ( approximately 50%). Very few in either group (<10%) had regular (<30 min variation) bedtimes or getting-up times. Compared to women with good sleep, those with insomnia reported drinking less caffeine per day, being more abstinent from alcohol, and having smaller variations in day-to-day alcohol intake and bedtimes. Although some women with insomnia limit or refrain from caffeine and alcohol intake, many have not optimized behaviors believed to help prevent or modulate insomnia.